Adam M. Brufsky, MD
Although metastatic breast cancer remains incurable for most women, recent research offers important new guidance for clinicians managing patients across the spectrum of advanced disease, according to a panel of experts participating in an OncLive Peer Exchange® program.
In the area of hormone receptor (HR)–positive breast cancer, study findings reported in recent months in journals and at the 2015 San Antonio Breast Cancer Symposium (SABCS) have helped refine the optimal use of endocrine therapies including strategies for combining these agents with targeted drugs.
The panel members, who are leading researchers in the breast cancer field, put these findings into context as part of a wide-ranging discussion of treatment options in a program entitled “Update on Advanced Breast Cancer Treatment.”
“Better understanding of breast cancer biology has led to important advances in terms of developing novel targeted and immune therapies,” said Adam M. Brufsky, MD, who served as program moderator. “… As novel agents for treating advanced breast cancer continue to evolve, we need to continue to learn how to best use them, how to optimally sequence them, and how to safely combine them.”
Clues on Low-Risk Disease
The panel first looked at the TAILORx low-risk registry,1
a prospective trial of endocrine therapy alone in patients with estrogen receptor (ER)– positive, HER2-negative, node-negative breast cancer. Of the 10,253 eligible patients enrolled, 1626 (15.9%) had favorable gene expression profiles. This was defined as <11 on the Oncotype
Dx Score which, Christy A. Russell, MD, pointed out, has been validated in women with ER-positive, HER2-negative, lymph node-negative breast cancer.
Findings on patients with these low scores have been published in The New England Journal of Medicine
Sparano et al showed that the risk of distant metastases from this primary cancer within 5 years is 1%. “There’s no way you’re ever going to be able to see a benefit from chemotherapy for that group, obviously, and it’s really extraordinary to see how well that group of women is doing,” said Russell.
Panel members pointed out that tools that would help predict metastasis frequently are not being used. “The underuse of Oncotype to me was shocking across this country and so you don’t know what people’s motivations are in ordering it or not ordering it,” said Russell. She noted that it might be a reasonable decision not to order it “in a very old population,” where you will not administer chemotherapy in any case.
Refining Use of Fulvestrant
In the metastatic disease setting, panel members discussed how best to deploy fulvestrant, which the FDA approved in 2002 for postmenopausal women with HR-positive metastatic breast cancer with disease progression following antiestrogen therapy. Brufsky commented that he hopes “we’re gaining a little bit more knowledge about how to use it properly.”
Recent studies have shown the proper dose that should be used for fulvestrant, said Sara A. Hurvitz, MD. The 250-mg dose used in the early studies required 3 or 4 months for adequate blood levels to be achieved, during which time patients were progressing and being switched to alternative therapies.
The CONFIRM study used 500-mg monthly and a loading dose given at day 14 of the first month and demonstrated a significant improvement in outcomes for patients in the metastatic setting.
More recently, for first-line treatment of metastatic ER-positive, postmenopausal breast cancer, the FIRST trial2 compared the 500-mg dose of fulvestrant plus a loading regimen with anastrozole. FIRST data showed that the time to progression was significantly improved with fulvestrant, and findings presented at SABCS 2014 demonstrated that overall survival was improved with fulvestrant. Other studies have demonstrated that fulvestrant is not the only option for these patients, Hurvitz noted. Palbociclib, a novel CDK 4/6 inhibitor, showed benefit in combination with letrozole in the phase II PALOMA-1 study in terms of progression- free survival (PFS) in the frontline setting. That combination was approved in February 2015. “We now have two regimens and we don’t have any way of comparing their relative efficacy, both based on phase II data, not on phase III,” Hurvitz said.
More answers are expected to come from the FALCON trial, which is comparing 500-mg fulvestrant with anastrozole as first-line hormonal therapy in postmenopausal women with locally advanced or metastatic, HR-positive breast cancer.
“We’re waiting for the phase III FALCON study to inform us about time-to-progression and overall survival with fulvestrant,” Hurvitz said. “But I don’t know whether it’s going to replace palbociclib in this setting.”